Induced pluripotent stem cell derived glial enriched progenitor cells for the treatment of white matter stroke

Abstract

In various embodiments methods and compositions for improving a recovery of a subject after a cerebral ischemic injury, such as white matter stroke are provided. In certain embodiments, the methods involve administering human induced pluripotent glial enriched progenitor cells into the brain of the subject.

What is claimed is: 
     
         1 . A method of improving recovery of a human after a subcortical white matter stroke (WMS), said method comprising
 (i) culturing human induced pluripotent stem cells (hiPSCs) in a culture medium containing basic fibroblast growth factor (FGF), retinoic acid (RA) and sonic hedgehog agonist to produce neural rosette that is then cultured in a neural progenitor cell (NPC) medium containing epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) to produce neural progenitor cells (NPCs);   (ii) culturing the NPCs of step (i) in said NPC medium containing 100 μM to 200 μM of deferoxamine (DFX) for 3 to 5 days to obtain glial-enriched progenitor cells (GEPs), wherein the GEPs exhibit an elevated expression of growth differentiation factor 15 (GDF15), growth differentiation factor 3 (GDF3) and vascular endothelial growth factor alpha (VEGFA) as compared to the NPC that are not treated with DFX; and wherein said GEPs differentiation potential is restricted to astrocytes expressing GFAP and S100B, and   iii) directly administering a therapeutically effective amount of the GEPs into or adjacent to at about 0.05 mm to about 3 mm from the infarct core in the brain of said human,   wherein said GEPs are administered during the early subacute time period after the white matter stroke; and   wherein said administration promotes neurological recovery and improves white matter preservation after the subcortical WMS.   
     
     
         2 . The method of  claim 1 , wherein said glial-enriched progenitor cells are administered directly into the infract core. 
     
     
         3 . The method of  claim 1 , wherein said glial-enriched progenitor cells are administered using a depot delivery system comprising a hydrogel.